We previously reported that posttransplant alloantibody production in CD8-deficient hosts is IL-4+CD4+ T cell-dependent and IgG1 isotype-dominant. The current studies investigated the hypothesis that IL-4-producing NKT cells contribute to maximal alloantibody production. To investigate this, alloantibody levels were examined in CD8-deficient wild-type, CD1d KO and Jα18 KO transplant recipients. We found that the magnitude of IgG1 alloantibody production was critically dependent on the presence of type I NKT cells, which are activated by day 1 posttransplant. Unexpectedly, type I NKT cell contribution to enhanced IgG1 alloantibody levels was IFN-γ-dependent and IL-4-independent. Cognate interactions between Type I NKT and B cells alone do not stimulate alloantibody production. Instead, NKT cells appear to enhance maturation of IL-4+CD4+ T cells. To our knowledge, this is the first report to substantiate a critical role for type I NKT cells in enhancing in vivo antibody production in response to endogenous antigenic stimuli.

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1. The spleen is an organ of multiple structures and many functions, but in the interests of human health and disease, it is probably far more important pathologically than physiologically. 2. It has been abundantly proved that instability in splenic functional balance toward any one of the essential elements of the blood passing through this organ may be an inherited trait, as in congenital hemolytic icterus. Recognition is now made of a syndrome in which, despite intensive compensatory panmyeloid hyperplasia, indiscriminate elimination of all circulating elements occurs, actually simulating panmyeloid hypoplasia. Splenectomy in such a syndrome is often dramatically curative. "Primary splenic panhematopenia" is suggested as an appropriate descriptive designation. 3. The potentially important role which may be played by the spleen, secondarily involved in a wide variety of syndromes, with the precipitation of varying degrees of peripheral cellular disequilibria, demands careful diagnostic discrimination. A dependable experience in the specific technics by which bone marrow and splenic functions are appraised is essential to sound judgment and clinical acumen. 4. The normal spleen is apparently not essential to life and health at any age and, therefore, may be surgically removed without prejudice to future hemolytopoietic equilibria and longevity. The pathologic spleen may at times constitute a very real hazard to health and an actual threat to survival; in the more acute syndromes, prompt surgical intervention may be lifesaving.

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1. Rabbits were immunized with both normal (Nrbc) and trypsinized (Trbc) human red blood cells and the antisera examined with normal, trypsinized, periodate-treated, and hemolytic anemia cells. 2. Absorption studies showed the presence of a fraction in both anti-Trbc and anti-Nrbc that was specific for trypsinized cells. 3. This T cell specific fraction from anti-Trbc serum (anti-TE) did not agglutinate or sensitize normal red blood cells, but agglutinated periodate-treated cells. This latter specificity was shown to be a part of the modification produced by trypsinization. 4. Anti-TE also agglutinated the cells of fifteen of nineteen patients with acquired hemolytic anemia and three of thirteen cases of hereditary spherocytosis. 5. Antibody for trypsinized and normal cells was also detected in antiserum to normal cells. Absorption data suggested the presence in this antiserum of antibody with a dual specificity for both types of cells. 6. The role of the antigenic modifications produced by trypsin in red cell immunization and in hemolytic anemia is discussed.