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CD45RC isoforms define two types of CD4 memory T cells, one of which depends on persisting antigen.

Bunce C, Bell EB - J. Exp. Med. (1997)

Bottom Line: DNCB-specific activity was now found wholly within the CD45RC+ "revertant" subset; the CD45RC-CD4 T cell population was devoid of activity.Importantly, we found that the total switch-back from CD45RC- to RC+ could be prevented, apparently by persisting antigen.The results indicate that there are two functionally distinct categories of memory T cells: one, a short-lived CD45Rlow type which orchestrates the rapid kinetics, the other, a longer-lived CD45Rhigh revertant which ensures that immunological memory endures.

View Article: PubMed Central - PubMed

Affiliation: Immunology Research Group, Biological Sciences, University of Manchester, United Kingdom.

ABSTRACT
The cellular basis of immunological memory remains a controversial area with respect to the identity of memory T cells and the role of persisting antigen. CD4 T cells are phenotypically divided by the expression of high and low molecular weight isoforms of CD45, surface markers that are frequently used to identify "naive" (CD45Rhigh) and "memory" (CD45Rlow) subsets. The latter subset responds rapidly in antigen recall assays but paradoxically has a short life span, a property that is difficult to reconcile with long-term memory. The present study examines these issues using a DTH (delayed-type hypersensitivity) model in which contact sensitivity to dinitrochlorobenzene (DNCB) was transferred to athymic nude rats by recirculating CD4 T cell subsets defined in the rat by the anti-CD45RC mAb OX22. As expected, CD45RC+ (but not RC-) CD4 T cells from normal unprimed rats transferred a DNCB-specific DTH response, whereas, 4 d after sensitization the CD45RC- (memory) subset alone contained the DNCB reactivity. However, when donor cells were collected from thymectomized rats sensitized two mo earlier, DNCB-specific responses were transferred by both CD45RC- and RC+ subsets suggesting that many of the latter had developed from cells with a memory phenotype. This was confirmed when CD45RC CD4 T cells from 4-d primed rats were parked in intermediate nude recipients and recovered 2 mo later. DNCB-specific activity was now found wholly within the CD45RC+ "revertant" subset; the CD45RC-CD4 T cell population was devoid of activity. Importantly, we found that the total switch-back from CD45RC- to RC+ could be prevented, apparently by persisting antigen. The results indicate that there are two functionally distinct categories of memory T cells: one, a short-lived CD45Rlow type which orchestrates the rapid kinetics, the other, a longer-lived CD45Rhigh revertant which ensures that immunological memory endures.

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Donor-derived CD4 T cells infiltrate the ears of DNCB-challenged, T cell reconstituted nude rats. Ears from uninjected nude rats (Control)  or from nude rats injected with CD45RC+ revertants or with unresponsive CD45RC− T cells (all taken from rats of experiment Fig. 3a at 48 h) were snap  frozen, sectioned, and stained for the presence of RT7b allotype-marked donor cells as described elsewhere (50). There was a heavy infiltrate of donorderived CD4 T cells in the dermis (de) and epidermis (ep) of recipients reconstituted with CD45RC+ revertant T cells and the surface of the epidermis  showed necrotic foci (*) containing numerous polymorphonuclear leukocytes. In cross section, the ears were swollen, more cellular, and increased in  thickness compared with ears from control and CD45RC− T cell–injected nude rats (insets). The ears of the latter recipients showed a modest infiltrate of  donor-derived cells but were not swollen. Original magnification ×80; inset ×10. cu, cutis; ca, cartilage; mu, muscle. The immunostaining and photographs were kindly provided by K. Bankes-John and Jürgen Westermann, Hannover, Germany.
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Figure 4: Donor-derived CD4 T cells infiltrate the ears of DNCB-challenged, T cell reconstituted nude rats. Ears from uninjected nude rats (Control) or from nude rats injected with CD45RC+ revertants or with unresponsive CD45RC− T cells (all taken from rats of experiment Fig. 3a at 48 h) were snap frozen, sectioned, and stained for the presence of RT7b allotype-marked donor cells as described elsewhere (50). There was a heavy infiltrate of donorderived CD4 T cells in the dermis (de) and epidermis (ep) of recipients reconstituted with CD45RC+ revertant T cells and the surface of the epidermis showed necrotic foci (*) containing numerous polymorphonuclear leukocytes. In cross section, the ears were swollen, more cellular, and increased in thickness compared with ears from control and CD45RC− T cell–injected nude rats (insets). The ears of the latter recipients showed a modest infiltrate of donor-derived cells but were not swollen. Original magnification ×80; inset ×10. cu, cutis; ca, cartilage; mu, muscle. The immunostaining and photographs were kindly provided by K. Bankes-John and Jürgen Westermann, Hannover, Germany.

Mentions: The ears of DNCB challenged nude recipients were examined immunohistochemically for the presence of donor-derived CD4 T cells, i.e., those staining positive for the RT7b allotype marker. Representative samples from the experiment in Fig. 3 a are illustrated in Fig 4. The ears of uninjected nude controls, which showed no net increase in ear thickness, were devoid of allotypemarked cells. In contrast, recipients' ears of CD45RC+ revertants were heavily infiltrated; donor T cells were abundant in the greatly thickened dermis and epidermis. Curiously, all samples in this group had numerous consolidated foci on the outer surface of the epidermis containing dense collections of polymorphonuclear leukocytes. The increased ear thickness, induced by the CD45RC+ revertants and measured in situ, was clearly visible in cross section (Fig. 4, insets). The ears of nude rats injected with nonresponsive CD45RC− CD4 T cells, lacking DNCB-specific T cells, were also infiltrated with donor-derived CD4 T cells, but to a lesser extent. Clearly, both DNCB-specific and nonspecific CD4 T cells had ready access to the ear, but only the former induced changes (presumably by cytokine release) that caused a local increase in ear thickness.


CD45RC isoforms define two types of CD4 memory T cells, one of which depends on persisting antigen.

Bunce C, Bell EB - J. Exp. Med. (1997)

Donor-derived CD4 T cells infiltrate the ears of DNCB-challenged, T cell reconstituted nude rats. Ears from uninjected nude rats (Control)  or from nude rats injected with CD45RC+ revertants or with unresponsive CD45RC− T cells (all taken from rats of experiment Fig. 3a at 48 h) were snap  frozen, sectioned, and stained for the presence of RT7b allotype-marked donor cells as described elsewhere (50). There was a heavy infiltrate of donorderived CD4 T cells in the dermis (de) and epidermis (ep) of recipients reconstituted with CD45RC+ revertant T cells and the surface of the epidermis  showed necrotic foci (*) containing numerous polymorphonuclear leukocytes. In cross section, the ears were swollen, more cellular, and increased in  thickness compared with ears from control and CD45RC− T cell–injected nude rats (insets). The ears of the latter recipients showed a modest infiltrate of  donor-derived cells but were not swollen. Original magnification ×80; inset ×10. cu, cutis; ca, cartilage; mu, muscle. The immunostaining and photographs were kindly provided by K. Bankes-John and Jürgen Westermann, Hannover, Germany.
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Related In: Results  -  Collection

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Figure 4: Donor-derived CD4 T cells infiltrate the ears of DNCB-challenged, T cell reconstituted nude rats. Ears from uninjected nude rats (Control) or from nude rats injected with CD45RC+ revertants or with unresponsive CD45RC− T cells (all taken from rats of experiment Fig. 3a at 48 h) were snap frozen, sectioned, and stained for the presence of RT7b allotype-marked donor cells as described elsewhere (50). There was a heavy infiltrate of donorderived CD4 T cells in the dermis (de) and epidermis (ep) of recipients reconstituted with CD45RC+ revertant T cells and the surface of the epidermis showed necrotic foci (*) containing numerous polymorphonuclear leukocytes. In cross section, the ears were swollen, more cellular, and increased in thickness compared with ears from control and CD45RC− T cell–injected nude rats (insets). The ears of the latter recipients showed a modest infiltrate of donor-derived cells but were not swollen. Original magnification ×80; inset ×10. cu, cutis; ca, cartilage; mu, muscle. The immunostaining and photographs were kindly provided by K. Bankes-John and Jürgen Westermann, Hannover, Germany.
Mentions: The ears of DNCB challenged nude recipients were examined immunohistochemically for the presence of donor-derived CD4 T cells, i.e., those staining positive for the RT7b allotype marker. Representative samples from the experiment in Fig. 3 a are illustrated in Fig 4. The ears of uninjected nude controls, which showed no net increase in ear thickness, were devoid of allotypemarked cells. In contrast, recipients' ears of CD45RC+ revertants were heavily infiltrated; donor T cells were abundant in the greatly thickened dermis and epidermis. Curiously, all samples in this group had numerous consolidated foci on the outer surface of the epidermis containing dense collections of polymorphonuclear leukocytes. The increased ear thickness, induced by the CD45RC+ revertants and measured in situ, was clearly visible in cross section (Fig. 4, insets). The ears of nude rats injected with nonresponsive CD45RC− CD4 T cells, lacking DNCB-specific T cells, were also infiltrated with donor-derived CD4 T cells, but to a lesser extent. Clearly, both DNCB-specific and nonspecific CD4 T cells had ready access to the ear, but only the former induced changes (presumably by cytokine release) that caused a local increase in ear thickness.

Bottom Line: DNCB-specific activity was now found wholly within the CD45RC+ "revertant" subset; the CD45RC-CD4 T cell population was devoid of activity.Importantly, we found that the total switch-back from CD45RC- to RC+ could be prevented, apparently by persisting antigen.The results indicate that there are two functionally distinct categories of memory T cells: one, a short-lived CD45Rlow type which orchestrates the rapid kinetics, the other, a longer-lived CD45Rhigh revertant which ensures that immunological memory endures.

View Article: PubMed Central - PubMed

Affiliation: Immunology Research Group, Biological Sciences, University of Manchester, United Kingdom.

ABSTRACT
The cellular basis of immunological memory remains a controversial area with respect to the identity of memory T cells and the role of persisting antigen. CD4 T cells are phenotypically divided by the expression of high and low molecular weight isoforms of CD45, surface markers that are frequently used to identify "naive" (CD45Rhigh) and "memory" (CD45Rlow) subsets. The latter subset responds rapidly in antigen recall assays but paradoxically has a short life span, a property that is difficult to reconcile with long-term memory. The present study examines these issues using a DTH (delayed-type hypersensitivity) model in which contact sensitivity to dinitrochlorobenzene (DNCB) was transferred to athymic nude rats by recirculating CD4 T cell subsets defined in the rat by the anti-CD45RC mAb OX22. As expected, CD45RC+ (but not RC-) CD4 T cells from normal unprimed rats transferred a DNCB-specific DTH response, whereas, 4 d after sensitization the CD45RC- (memory) subset alone contained the DNCB reactivity. However, when donor cells were collected from thymectomized rats sensitized two mo earlier, DNCB-specific responses were transferred by both CD45RC- and RC+ subsets suggesting that many of the latter had developed from cells with a memory phenotype. This was confirmed when CD45RC CD4 T cells from 4-d primed rats were parked in intermediate nude recipients and recovered 2 mo later. DNCB-specific activity was now found wholly within the CD45RC+ "revertant" subset; the CD45RC-CD4 T cell population was devoid of activity. Importantly, we found that the total switch-back from CD45RC- to RC+ could be prevented, apparently by persisting antigen. The results indicate that there are two functionally distinct categories of memory T cells: one, a short-lived CD45Rlow type which orchestrates the rapid kinetics, the other, a longer-lived CD45Rhigh revertant which ensures that immunological memory endures.

Show MeSH
Related in: MedlinePlus