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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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The kinetics of the DNCB response in once- or twiceprimed rats is similar. Rats were sensitized with DNCB on day 0 and earchallenged at various times after sensitization (closed circles) or were sensitized with DNCB a second time at 6.5 wk (open triangles) or 8 wk (open  circles) and ear-challenged at the times indicated. Each point is the mean ±  SD of 3–5 rats. The twice-primed rats were thymectomized before sensitization.
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Figure 5: The kinetics of the DNCB response in once- or twiceprimed rats is similar. Rats were sensitized with DNCB on day 0 and earchallenged at various times after sensitization (closed circles) or were sensitized with DNCB a second time at 6.5 wk (open triangles) or 8 wk (open circles) and ear-challenged at the times indicated. Each point is the mean ± SD of 3–5 rats. The twice-primed rats were thymectomized before sensitization.

Mentions: An important question arises as to whether CD45RC+ revertants display characteristics similar to or different from truly naive antigen-inexperienced CD45RC+ T cells. Available evidence suggests that CD45RC+ “revertants” behaved like unprimed T cells. For example, when revertants were collected from 2-mo primed thymectomized rats, transferred to nude recipients and challenged immediately (a measure of effector cell potential), they were unable to evoke a DTH response (CD45RC+: 74 μm ± 17; control: 62 μm ± 15). In addition, the kinetics of the DTH response in sensitized rats was comparable with that of rats resensitized 6.5 or 8 wk after primary sensitization. Once- or twice-primed rats were ear challenged on various days after sensitization. When compared with the once-primed animals, the kinetics of the DNCB responses in twice-primed rats were remarkably similar (Fig. 5). The peak responses occurred at day 4 in both once- and twice-primed rats suggesting, but not proving, that CD45RC+ revertants responded with primary kinetics. There was, however, a significant increase in the response at day 3 after secondary sensitization (P <0.001). Although not proven, this early increase could be due to DNCB-specific CD45RC− CD4 T cells in sensitized rats being retained in an upregulated state by persisting antigen.


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)

The kinetics of the DNCB response in once- or twiceprimed rats is similar. Rats were sensitized with DNCB on day 0 and earchallenged at various times after sensitization (closed circles) or were sensitized with DNCB a second time at 6.5 wk (open triangles) or 8 wk (open  circles) and ear-challenged at the times indicated. Each point is the mean ±  SD of 3–5 rats. The twice-primed rats were thymectomized before sensitization.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196145&req=5

Figure 5: The kinetics of the DNCB response in once- or twiceprimed rats is similar. Rats were sensitized with DNCB on day 0 and earchallenged at various times after sensitization (closed circles) or were sensitized with DNCB a second time at 6.5 wk (open triangles) or 8 wk (open circles) and ear-challenged at the times indicated. Each point is the mean ± SD of 3–5 rats. The twice-primed rats were thymectomized before sensitization.
Mentions: An important question arises as to whether CD45RC+ revertants display characteristics similar to or different from truly naive antigen-inexperienced CD45RC+ T cells. Available evidence suggests that CD45RC+ “revertants” behaved like unprimed T cells. For example, when revertants were collected from 2-mo primed thymectomized rats, transferred to nude recipients and challenged immediately (a measure of effector cell potential), they were unable to evoke a DTH response (CD45RC+: 74 μm ± 17; control: 62 μm ± 15). In addition, the kinetics of the DTH response in sensitized rats was comparable with that of rats resensitized 6.5 or 8 wk after primary sensitization. Once- or twice-primed rats were ear challenged on various days after sensitization. When compared with the once-primed animals, the kinetics of the DNCB responses in twice-primed rats were remarkably similar (Fig. 5). The peak responses occurred at day 4 in both once- and twice-primed rats suggesting, but not proving, that CD45RC+ revertants responded with primary kinetics. There was, however, a significant increase in the response at day 3 after secondary sensitization (P <0.001). Although not proven, this early increase could be due to DNCB-specific CD45RC− CD4 T cells in sensitized rats being retained in an upregulated state by persisting antigen.

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