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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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Evidence that antigen-experienced  DNCB-specific CD45RC− CD4 T cells revert to a  CD45RC+ phenotype in DNCB-sensitized rats.  Donor rats (thymectomized) were sensitized with  DNCB, TDL collected 2 mo (a, b) or 4 d (c, d) later,  separated into CD45RC+ and CD45RC− subsets  and 10 × 106 (or 50 × 106 as indicated) T cells transferred to athymic nude rats. Recipients were reconstituted for 3 wk (b) or for 2 mo (d), sensitized, earchallenged 4 d later and ear thickness measured after  24 h. Histograms represent means ± SD of 3 or 4  rats in each group. Test of significance: (b)  CD45RC+ vs CD45RC−, P <0.02.
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Figure 2: Evidence that antigen-experienced DNCB-specific CD45RC− CD4 T cells revert to a CD45RC+ phenotype in DNCB-sensitized rats. Donor rats (thymectomized) were sensitized with DNCB, TDL collected 2 mo (a, b) or 4 d (c, d) later, separated into CD45RC+ and CD45RC− subsets and 10 × 106 (or 50 × 106 as indicated) T cells transferred to athymic nude rats. Recipients were reconstituted for 3 wk (b) or for 2 mo (d), sensitized, earchallenged 4 d later and ear thickness measured after 24 h. Histograms represent means ± SD of 3 or 4 rats in each group. Test of significance: (b) CD45RC+ vs CD45RC−, P <0.02.

Mentions: Investigations based on whole cell populations, but with no regard for antigen specificity, have indicated that CD45RC− T cells (and comparable CD45RA− RO+ T cells in humans) will reexpress with time the high molecular weight isoform (CD45RC+ in rats; CD45RA+ in humans) both in vitro (46–49) and in vivo (27–29, 34, 45). However, there is no clear demonstration that such a reversion (from a memory to a naive phenotype) will occur within an antigen-specific population in vivo. Therefore, we determined whether DNCB-specific memory T cells remained CD45RC− or could revert to CD45RC+ with time. To exclude a contribution of newly generated naive CD45RC+ CD4 T cells from the thymus, animals were thymectomized. 2 mo after sensitization, CD45RC+ and RC− subsets were obtained from TDL and adoptively transferred to nude recipients (Fig. 2 a). Over half the DNCB-specific activity was now found within the CD45RC+ subset (Fig. 2 b), suggesting that antigen-specific T cells had switched back from a CD45RC− state. It was also clear that at 2 mo, the CD45RC− subset still retained a large population of DNCB-specific T cells.


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)

Evidence that antigen-experienced  DNCB-specific CD45RC− CD4 T cells revert to a  CD45RC+ phenotype in DNCB-sensitized rats.  Donor rats (thymectomized) were sensitized with  DNCB, TDL collected 2 mo (a, b) or 4 d (c, d) later,  separated into CD45RC+ and CD45RC− subsets  and 10 × 106 (or 50 × 106 as indicated) T cells transferred to athymic nude rats. Recipients were reconstituted for 3 wk (b) or for 2 mo (d), sensitized, earchallenged 4 d later and ear thickness measured after  24 h. Histograms represent means ± SD of 3 or 4  rats in each group. Test of significance: (b)  CD45RC+ vs CD45RC−, P <0.02.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196145&req=5

Figure 2: Evidence that antigen-experienced DNCB-specific CD45RC− CD4 T cells revert to a CD45RC+ phenotype in DNCB-sensitized rats. Donor rats (thymectomized) were sensitized with DNCB, TDL collected 2 mo (a, b) or 4 d (c, d) later, separated into CD45RC+ and CD45RC− subsets and 10 × 106 (or 50 × 106 as indicated) T cells transferred to athymic nude rats. Recipients were reconstituted for 3 wk (b) or for 2 mo (d), sensitized, earchallenged 4 d later and ear thickness measured after 24 h. Histograms represent means ± SD of 3 or 4 rats in each group. Test of significance: (b) CD45RC+ vs CD45RC−, P <0.02.
Mentions: Investigations based on whole cell populations, but with no regard for antigen specificity, have indicated that CD45RC− T cells (and comparable CD45RA− RO+ T cells in humans) will reexpress with time the high molecular weight isoform (CD45RC+ in rats; CD45RA+ in humans) both in vitro (46–49) and in vivo (27–29, 34, 45). However, there is no clear demonstration that such a reversion (from a memory to a naive phenotype) will occur within an antigen-specific population in vivo. Therefore, we determined whether DNCB-specific memory T cells remained CD45RC− or could revert to CD45RC+ with time. To exclude a contribution of newly generated naive CD45RC+ CD4 T cells from the thymus, animals were thymectomized. 2 mo after sensitization, CD45RC+ and RC− subsets were obtained from TDL and adoptively transferred to nude recipients (Fig. 2 a). Over half the DNCB-specific activity was now found within the CD45RC+ subset (Fig. 2 b), suggesting that antigen-specific T cells had switched back from a CD45RC− state. It was also clear that at 2 mo, the CD45RC− subset still retained a large population of DNCB-specific T cells.

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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Related in: MedlinePlus