Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 91

Tabl e 3. 9. Leukocyte sources of cytokines, especially type-1 and -2 immunocytokines ( Part 1 ;
Sources: [ 175 , 928 ]). Cytokines can be classified into type-1 cytokines (IL2, IL12, IL18, Ifn γ ,

TGF [or TNFSF2]) that promote cellular immune response and type-2 cytokines

(IL4, IL5, IL6, IL9, IL10, IL13, and IL25, as well as granulocyte-macrophage colony-stimulating
factor [gmCSF or CSF2]) that favor humoral (antibody-mediated) immune response. Type-2
response is defined as an attenuated cellular response, but with a strong B-cell activity such as
hypergammaglobulinemia and an increase in the level of type-2 cytokines. Type-1 and -2 cytokines
then refer to cytokines produced by CD8

β ,TNF α and - β

type-1 effector T cells, such as type-1
cytotoxic (T C1 ) and helper T (T H1 ) cells, respectively, and type-2 effector T lymphocytes (T C2
and T H2 , respectively), respectively. Some of these type-1 and -2 cytokines are cross-regulatory:
interferon-

+ and CD4 +

and interleukin-12 decrease the concentrations of type-2 cytokines, whereas IL4 and
IL10 reduce the levels of type-1 cytokines. Type-1 cytokines, such as interferon-

γ

γ produced in

particular by CD8 type-1 effector T cells, interleukin-12 by antigen-presenting cells,

and IL18 by activated macrophages, are required for effective responses to intracellular pathogens
such as viruses. Type-2 cytokines produced by CD8

+ and CD4 +

type-2 effector T cells, mediate
allergic responses. On the other hand, class-1 cytokines comprise IL1 α and 1 β , IL2-IL7, IL9, IL11,
IL12a-IL12b, IL13, IL15, IL18, IL21, IL23, and IL33, CSF2, granulocyte colony-stimulating
factor (gCSF or CSF3), B-cell stimulating factor-3, leptin, erythropoietin, growth hormone, and
prolactin.

+ and CD4 +

Cell Cytokines

Type 1 Type 2

B cell IL12/18, TNF β IL6/10

NK cell Ifn γ ,TNF β

CD4 + T cell IL2/12, Ifn γ ,TNF β IL4/5/6/10/13

CD8 + T cell IL2, Ifn γ IL4/5/10

Basophils represent the main antigen-binding cell population in the bone marrow,
spleen, and blood after protein immunization. Their capacity to bind large amounts
of antigens on their surface depends on their expression of immunoglobulin-E
receptors and antigen-specific IgE produced by B cells after immunization [ 174 ].
Activated basophils express plasmalemmal receptors such as CD40L. Activated
basophils also enhance humoral memory B-cell responses by producing interleukin-
4 and -6 in response to specific antigens.
Basophils induce a T H2 phenotype in CD4 T lymphocytes, especially during

parasite infection and allergic inflammation. Basophils activate the production by
CD4

+

T cell of interleukins IL4, IL5, IL10, IL13, and transcription factor GATA3,
but downregulate interferon-

+

and IL2. Basophils synthesize both IL4 and thymic
stromal lymphopoietin to elicit T H2 immunity. In addition, T H2 differentiation
promoted by basophils involves intercellular contact with CD4

γ

+ T lymphocytes

in draining lymph nodes [ 173 ].
Human basophils, after IgE crosslinkage, secrete IL25 (or IL17e). IL25 stim-
ulates the production of T H2 cytokines IL4, IL5, and IL13 and recruitment of
eosinophils. IL25 can also activate T H2 memory T cells that strongly express IL25
receptor.