CD45 isoforms expression on CD4+ and CD8+ T cells throughout life, from newborns to centenarians: implications for T cell memory

Cossarizza, Andrea; Ortolani, Claudio; Paganelli, Roberto; Barbieri, Daniela; Monti, Daniela; Sansoni, Paolo; Fagiolo, U; Castellani, Gastone; Bersani, Ferdinando; Londei, Marco; Franceschi, Claudio

doi:10.1016/0047-6374(95)01691-0

Cited by 241 publications

(161 citation statements)

References 80 publications

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“…Consistent with stronger CD45RA expression on CD8 þ versus CD4 þ T cells, 8 the procedure relatively increased the CD4/CD8 ratio. T cells in final products were predominantly of CD45RA À effector memory and central memory phenotype, whereas those of CD45RA þ naive or late effector differentiation were completely removed.…”

Section: Discussionsupporting

confidence: 48%

Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis

Teschner

Distler

Wehler

et al. 2013

Bone Marrow Transplant

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Depletion of naive T cells from donor leukapheresis products (LPs) aims at the reduction of alloreactivity, while preserving memory T-cell reactivity (for example, to pathogens). This study established the immunomagnetic depletion procedure under clean room conditions using CD45RA beads and analyzed LPs of six donors for cell composition and functional immune responses. CD45RA depletion resulted in 3.4-4.7 log (median 4.4) reduction of CD45RA þ T cells, thereby eliminating naive and late effector T cells. B cells were also completely removed, whereas significant proportions of NK cells, monocytes and granulocytes persisted. CD45RA-depleted LPs contained effector and central memory CD4 þ and CD8 þ T cells that showed sustained IFN-g secretion to CMV, EBV, Aspergillus and Candida Ags. Alloreactivity was measured in MLRs between donors with complete HLA-mismatch. Alloreactive CD8 þ T cells were strongly reduced (median 41-log) upon CD45RA depletion, whereas alloreactive CD4 þ T cells persisted in significant numbers. In conclusion, clinical grade depletion of CD45RA þ naive T cells from donor LPs is feasible and highly efficient. The depleted products show sustained CD4 þ and CD8 þ T-cell reactivity to pathogens and effectively reduced CD8-mediated alloreactivity. Prophylactic and preemptive infusions after allogeneic SCT may improve T-cell reconstitution and pathogen-specific immunosurveillance, along with lower risk of inducing GVHD.

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Section: Discussionsupporting

confidence: 48%

Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis

Teschner

Distler

Wehler

et al. 2013

Bone Marrow Transplant

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“…The assumption always has been that these markers define Agexperienced T cells. Also, it is well established that there is an overall increase in the number of T cells with "memory" markers and also outgrowth of certain oligoclonal T cell populations during aging (21)(22)(23)(24). Once again, it is generally believed that this is due to Ag-driven expansion of T cells and represents the cumulative sum of the response to pathogens we encounter over a lifetime.…”

Section: Resultsmentioning

confidence: 99%

Cutting Edge: Naive T Cells Masquerading as Memory Cells

Murali‐Krishna

Ahmed

2000

The Journal of Immunology

430

399

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This study shows that naive CD8 T cells can acquire characteristics of memory T cells in the absence of stimulation with specific Ag simply by the process of homeostatic proliferation under lymphopenic conditions. This Ag-independent T cell differentiation pathway did not result in up-regulation of early activation markers (CD69, CD25, CD71), but expression of several memory markers (CD44, CD122, Ly6C) increased progressively with successive divisions. These markers were then stably expressed, and these cells also became more responsive functionally to specific Ag. Thus, all “memory” phenotype T cells in an individual may not be true Ag-experienced cells and may include naive cells masquerading as memory cells. These findings are specially relevant in cases of disease or treatment-induced lymphopenia such as in HIV-infected individuals or transplant recipients. In addition, this study may have implications for autoimmunity because homeostatic proliferation of naive T cells requires interaction with self peptide plus MHC molecules.

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“…The same can be observed in centenarians in good health conditions, who have some types of immune response which are well preserved (Mariotti et al, 1992;Sansoni et al, 1993;Cossarizza et al, 1996;Candore et al, 1997;Bagnara et al, 2000;Listì et al, 2006).…”

Section: Ageing and Longevity: The Demographic Revolutionmentioning

confidence: 66%