PMID- 8093257
OWN - NLM
STAT- MEDLINE
DCOM- 19930125
LR  - 20171116
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 150
IP  - 1
DP  - 1993 Jan 1
TI  - IL-2 reduces graft-versus-host disease and preserves a graft-versus-leukemia 
      effect by selectively inhibiting CD4+ T cell activity.
PG  - 197-205
AB  - We have recently demonstrated, in a fully MHC-mismatched murine bone marrow 
      transplantation model, that administration of a short course of high dose IL-2 
      markedly diminishes graft-vs-host disease (GVHD) without compromising 
      alloengraftment or the graft-vs-leukemia (GVL) effect of allogeneic T cells. We 
      have now evaluated the mechanism of the dissociation of GVL and GVHD observed in 
      this model. We demonstrate that CD4+ T cells were required to produce severe, 
      acute GVHD in the fully MHC-mismatched plus minor histocompatibility 
      Ag-mismatched A/J-->B10 strain combination. The GVHD-producing activity of A/J 
      CD4+ T cells administered without CD8+ T cells was inhibited by IL-2 treatment. 
      In contrast, CD8+ T cells alone mediated the GVL effect observed in the EL4 
      leukemia/lymphoma model, and CD4+ cells did not contribute to this effect. This 
      CD8-mediated GVL activity was not inhibited by IL-2 treatment. Because naive A/J 
      CD8+ T cells administered without CD4+ T cells did not produce acute GVHD, we 
      were unable to evaluate the effect of IL-2 in this model. However, when A/J 
      donors were presensitized with B10 skin grafts, CD4-depleted A/J spleen cells 
      were capable of causing acute GVHD in B10 recipients. This CD8-mediated GVHD was 
      not inhibited by treatment with IL-2. However, IL-2 did partially inhibit the 
      GVHD produced by nondepleted presensitized A/J spleen cells, probably due to 
      selective inhibition of the function of presensitized A/J CD4+ T cells. The 
      dissociation of GVHD and GVL against the EL4 leukemia/lymphoma in IL-2-treated 
      mice can therefore be explained by selective inhibition by IL-2 of CD4 activity.
FAU - Sykes, M
AU  - Sykes M
AD  - Transplantation Research Biology Center, Massachusetts General Hospital, Harvard 
      Medical School, Boston 02129.
FAU - Abraham, V S
AU  - Abraham VS
FAU - Harty, M W
AU  - Harty MW
FAU - Pearson, D A
AU  - Pearson DA
LA  - eng
GR  - R01CA55290/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CD4 Antigens)
RN  - 0 (CD8 Antigens)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-2)
SB  - IM
MH  - Animals
MH  - CD4 Antigens/physiology
MH  - CD4-Positive T-Lymphocytes/*drug effects/physiology
MH  - CD8 Antigens/analysis/physiology
MH  - Crosses, Genetic
MH  - Female
MH  - Graft vs Host Disease/immunology/*prevention & control
MH  - Immunosuppressive Agents/*pharmacology
MH  - Interleukin-2/*pharmacology
MH  - Leukemia, Experimental/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred A
MH  - Mice, Inbred C57BL
MH  - T-Lymphocyte Subsets/physiology
EDAT- 1993/01/01 00:00
MHDA- 1993/01/01 00:01
CRDT- 1993/01/01 00:00
PHST- 1993/01/01 00:00 [pubmed]
PHST- 1993/01/01 00:01 [medline]
PHST- 1993/01/01 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1993 Jan 1;150(1):197-205.